TY  - JOUR
A1  - Kaluzki, Irina
A1  - Hailemariam-Jahn, Tsige
A1  - Doll, Monika
A1  - Kaufmann, Roland
A1  - Balermpas, Panagiotis
A1  - Zöller, Nadja Nicole
A1  - Kippenberger, Stefan
A1  - Meissner, Markus
T1  - Dimethylfumarate inhibits colorectal carcinoma cell proliferation: Evidence for cell cycle arrest, apoptosis and autophagy
T2  - Cells
N2  - Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)-assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct anti-tumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.
KW  - dimethylfumarate
KW  - colorectal carcinoma
KW  - p21
KW  - cell cycle arrest
KW  - cyclin D1
KW  - p62
KW  - LC3 I/II
KW  - caspase-8
KW  - autophagy
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51774
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-517749
SN  - 2073-4409
N1  - This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
VL  - 8
IS  - 11, Art. 1329
SP  - 1
EP  - 14
PB  - MDPI
CY  - Basel
ER  -